储存血中泛素调节线粒体动态平衡对肿瘤细胞生物学特性的影响

与输血相关术后感染、肿瘤复发和生存率降低等严重影响肿瘤患者治疗效果，因此其中分子机制阐明是解决输血造成肿瘤不良预后关键所在。线粒体分裂融合是维持细胞代谢和生理过程重要组成，泛素正是此动态平衡关键调节因素。前期研究发现血液储存过程中随时间延长泛素浓度显著增加，而含高浓度泛素血清可明显促进肿瘤细胞增殖能力，据此推测血液储存过程中累积高浓度泛素可能通过调节线粒体动态平衡进而影响肿瘤细胞生物学特性。本课题拟从以下方面验证：1)从细胞水平，探讨储存血中泛素对肿瘤细胞生物学特性影响的线粒体动态平衡机制；2)动物模型试验验证泛素调节肿瘤组织线粒体动态平衡进而影响肿瘤进程；3) 收集肿瘤术前输血病例，验证储存血中泛素对肿瘤组织线粒体动态平衡调节是影响肿瘤输血治疗效果关键因素之一。预期结果将有助于进一步认识输血对于肿瘤不良预后发生机制，同时也为向临床提供更安全血液提供实验基础和理论依据。

Blood transfusion can induce infection，tumor recurrence and postoperative infection for tumor patients．Understanding the mechanisms of adverse clinical consequences of blood transfusion is paramount in developing safety treatment strategies for cancer. Ubiquitin can regulate mitochondrial dynamics, which is important to maintain homeostasis and physiological processes. Previous studies have found ubiquitin concentration increased in the plasma of whole blood during storage, which can significantly promote tumor cell proliferation. We propose ubiquitin accumulated in the blood during storage regulates mitochondrial dynamics to affect the tumor cells biological character. So the project will try to 1) explain mechanisms of ubiquitin regulate tumor cells biological function from the point of view of mitochondrial dynamics, 2) test the feasibility of ubiquitin affect tumor progression from regulating mitochondrial dynamics in mouse model, 3) demonstrate the effect ubiquitin on human cancer progression via regulating mitochondrial dynamics. Expected results will contribute not only to a better understanding of the adverse effects mechanisms of transfusion, but also provide experimental and theoretical basis for finding a new a safer blood.